Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells
Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells
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DOI：
10.1016/j.bcp.2007.02.012
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发表时间：
2007-06-30
影响因子：
5.8
通讯作者：
Park, Yeong-Min
中科院分区：
文献类型：
--
作者：
Lee, Jun Sik;Lee, Je Chul;Park, Yeong-Min
鲍曼不动杆菌是一种日益增多的医院获得性病原体，可导致各种类型的感染，但对这种微生物的保护性免疫反应知之甚少。鲍曼不动杆菌外膜蛋白A(AbOmpA)是一种主要的孔蛋白，在发病机制中起重要作用。我们分析了AbOmpA和树突状细胞(DC)之间的相互作用，以表征该蛋白在促进先天性和获得性免疫反应中的作用。AbOmpA通过增强表面标志CD40、CD54、B7家族(CD80和CD86)以及主要组织相容性复合体I、II类分子的表达来激活骨髓来源的DC。AbOmpA诱导DC产生Th1促进的白介素12，增强DC的同基因和同种异体免疫刺激能力。AbOmpA刺激混合淋巴细胞反应中T细胞产生干扰素-γ，提示Th1极化能力。经AbOmpA刺激的DC刺激的CD4(+)T细胞呈现Th1极化的细胞因子谱。树突状细胞表面标志物的表达受丝裂原活化蛋白激酶和核因子-kappaB途径的调节。我们的发现表明，AbOmpA诱导DC成熟并驱动Th1极化，这是确定鲍曼不动杆菌免疫应答性质的重要特性。(C)2007 Elsevier Inc.保留所有权利。
Acinetobacter baumannii is an increasing hospital-acquired pathogen that causes a various type of infections, but little is known about the protective immune response to this microorganism. Outer membrane protein A of A. baumannii (AbOmpA) is a major porin protein and plays an important role in pathogenesis. We analyzed interaction between AbOmpA and dendritic cells (DCs) to characterize the role of this protein in promoting innate and adaptive immune responses. AbOmpA functionally activates bone marrow-derived DCs by augmenting expression of the surface markers, CD40, CD54, B7 family (CD80 and CD86) and major histocompatibility complex class I and II. AbOmpA induces production of Th1-promoting interleukin-12 from DCs and augments the syngeneic and allogeneic immunostimulatory capacity of DCs. AbOmpA stimulates production of interferon-gamma from T cells in mixed lymphocyte reactions, which suggesting Th1-polarizing capacity. CD4(+) T cells stimulated by AbOmpA-stimulated DCs show a Thl-polarizing cytokine profile. The expression of surface markers on DCs is mediated by both mitogen-activated protein kinases and NF-kappa B pathways. Our findings suggest that AbOmpA induces maturation of DCs and drives Th1 polarization, which are important properties for determining the nature of immune response against A. baumannii. (c) 2007 Elsevier Inc. All rights reserved.